Experimental Oncology, 2009, № 3

DNA double strand breaks repair and apoptosis induction in peripheral blood lymphocytes of head and neck cancer patients

2009-01-01T00:00:00Z

DNA double strand breaks repair and apoptosis induction in peripheral blood lymphocytes of head and neck cancer patients Rusin, P.; Markiewicz, L.; Olszewski, J.; Morawiec-Sztandera, A.; Kowalski, M.; Przybylowska, K.; Kaczmarczyk, D.; Kusmierczyk, K.; Majstereksup, I. Aim: To evaluate the generation and repair of DNA double strand breaks (DSBs) as a critical factors that define the efficiency of radiation therapy of cancer patients. Methods: Peripheral blood lymphocytes obtained from 18 patients with head and neck squamous cell carcinoma (HNSCC) and 18 healthy donors were studied. The efficiency of DSBs repair after genotoxic treatment with hydrogen peroxide and γ-radiation were examined by neutral comet assay. MTT assay was used for cell viability analysis and Annexin V-FITC kit specific for kinase-3 was employed to determine apoptosis. Results: Lymphocytes from HNSCC patients were sensitive to genotoxic treatment and displayed impaired DSBs repair. Finally, as a consequence of this finding we have evidenced higher rate of apoptosis induction after γ-radiation treatment of lymphocytes from HNSCC patients than those from healthy controls. Conclusions: DSBs repair and increased apoptosis in cells of patients with head and neck cancer is relevant for efficient therapy of HNSCC.

Helicobacter pylori infection of gastric cancercells elevates the level of expression and activation of protein kinase D2

2009-01-01T00:00:00Z

Helicobacter pylori infection of gastric cancercells elevates the level of expression and activation of protein kinase D2 Shabelnik, M.Yu; Kostyuk, O.V.; Merentsev, S.V.; Tarasova, T.O.; Sidorenko, S.P. Aim: To test the hypothesis, whether H. pylori infection may affect the level of PKD2 expression and/or activation in gastric cancer cells. Methods: Studies were performed on AGS human gastric adenocarcinoma cell line, gastric tissues samples from 36 cases of different histological variants of gastric cancer. Immunohistochemical, cell and molecular biology, bacteriological and biochemical approaches have been used in this study. Results: H. pylori 16S rRNA gene was detected in 97% cases of gastric tumors, and in 83% of cases cаgA gene was detected. In all tested adenocarcinoma samples cagA+ H. pylori was revealed. These cases were characterized by high level of PKD1/2 expression and autophosphorylation. In adenogenic cancer samples the presence of cagA– H. pylori was identified. Carcinoid and nondifferentiated gastric cancers contain H. pylori, with very low numbers of cagA+ copies. All cases of gastric tumors with cagA– H. pylori had very low levels of PKD1/2 autophosphorylation. AGS cell line infection with cagA– and cagA+ H. рylori resulted in elevation of PKD2 expression levels in 3.29 and 3.66 times respectively (p < 0.001). In cells infected by cag+ H. рylori the level of PKD2 transphosphorylation was 1.39 higher than in cells infected by cagA– H. pylori. For PKD2 autophosphorylation this difference was even higher — 3.27 times (p < 0.001). Conclusion: H. pylori infection enhanced the level of protein kinase D2 expression, trans- and autophosphorylation. The level of PKD2 autophosphorylation/activation was higher in AGS cell line inoculated of with cag+ H. pylori than in AGS cells with cagA– H. pylori. These suggest that H. pylori induces activation of PKD1/2 and could exploit PKD2 mediated signaling pathways that may contribute to the pathogenesis of gastric cancer.

Postoperative autovaccinotherapy for patients with gastric cancer and expression of some proteins in tumor tissue

2009-01-01T00:00:00Z

Postoperative autovaccinotherapy for patients with gastric cancer and expression of some proteins in tumor tissue Bazas, V.M.; Lukyanova, N.Yu.; Lisovenko, G.S.; Rozumiy, D.O.; Potebnya, G.P. Aim: To study the efficacy of autovaccine in the treatment of gastric cancer and significance of molecular factors having prognostic values for disease outcome to evaluate its efficacy in clinical setting. Patients and Methods: 150 patients with histologically proven adenocarcinoma of the stomach of stages II, III or IV were enrolled into study. 86 patients have been treated with autovaccine (AV) after operation. Expression of p53, Bcl-2, receptors of tyrosine kinase, vascular endothelial growth factor (VEGF), Е-cadherin, α-catenin and β-catenin was determined in paraffin embedded tumor samples by means of immunohistochemical method with the use of respective monoclonal antibodies. Results: It was shown that application of AV has resulted in the increase of 3-year overall survival of patients having stage III of disease by more than 30%, but those having stage IV — only around 14%. The increase of 3-year overall survival of patients with metastases in lymph nodes (N1–2) was observed also in more than 30%. It has been suggested the optimal phenotype for vaccine application: р53(+), EGFR(+), HER-2 neu (+), β-catenin (+), VEGF(+) and Bcl-2(+) with no dependence on E-cadherin and α-catenin presence. Conclusion: It was determined that the best effect of AV application is observed in patients with category Т3–4, poorly-differentiated tumors, metastases in lymph nodes (N1–2), but without distant metastases (М0). Gastric cancer patients with p53, EGFR, HER-2/neu, β-catenin, VEGF and Bcl-2-positive tumors are the favorable group for the treatment with AV in the adjuvant regime.

Vascular endothelial growth factor exression in uterine cervical cancer: correlation with clinicopathologic characteristics and survival

2009-01-01T00:00:00Z

Vascular endothelial growth factor exression in uterine cervical cancer: correlation with clinicopathologic characteristics and survival Goncharuk, I.V.; Vorobjova, L.I.; Lukyanova, N.Yu.; Chekhun, V.F. Aim: This retrospective study was performed to determine the vascular endothelial growth factor (VEGF) expression in cervical cancer cells, and to examine its correlation with clinicopathologic characteristics and survival of patients. Methods: Seventy-five paraffinembedded primary tumors were stained immunohistochemically for VEGF expression, which was analysed semiquantitatively. Results: The significant correlation between VEGF expression and stages of disease, as well as pelvic lymph node metastasis was observed. There were determined a negative correlations between VEGF expression in tumor cells and both overall and disease-free survival. Conclusion: VEGF expression in human cervical cancer may be used as a diagnostic parameter in the clinic. Our results are in accordance with literature data showing association of VEGF overexpression in tumor with a poorer patient survival.